Vers une éducation médicale axée sur les compétences dans le domaine de la psychiatrie des toxicomanies: une revue systématique

Background: Current curriculum guidelines for addiction training in psychiatry need to be adapted to the competency by design framework to integrate clinical skills in addiction. Objective: We conducted a systematic review to identify curricular and educational interventions to build competency among psychiatry residents and fellows in addiction psychiatry. Methods: We followed the PRISMA guidelines, searching five databases from inception to August 2020 for relevant evaluation-type studies exploring addiction psychiatry competency among psychiatry residents and fellows. We appraised study quality using the Joanna Briggs Institute's risk of bias tool for observational designs. Results: From 1600 records, 17 studies met inclusion criteria. Addiction psychiatry competencies spanned themes involving core knowledge development; attitudinal, communication and leadership skills; screening, assessment, diagnosis; management; and special populations. Examples of effective educational interventions to enhance addiction competency include specific modules for substance use disorders and integrated clinical rotations that simultaneously combine multiple types of skills. Lived experience improved trainee attitudes towards addiction psychiatry. Conclusions: While there is current evidence supporting strategies for developing competency in addiction psychiatry, the lack of studies measuring sustained competence over a longer-term follow-up period and the absence of randomized controlled trials limit the overall strength of evidence in this review. Current psychiatry entrustable professional activities (EPAs) involving addiction only partly overlap with curriculum training guidelines and studies identified in this review. These EPAs need to be better identified for training programs, competence in those EPAs better delineated for residents and preceptors, and evaluations should be done to ensure that adequate competence in addictions is attained and sustained.Contexte : Les directives actuelles du programme d’études pour la formation sur les toxicomanies en psychiatrie doivent être adaptées au cadre de la CPC pour intégrer les compétences cliniques en toxicomanie. Objectif : Nous avons effectué une revue systématique de la littérature afin de repérer les interventions éducatives visant à renforcer les compétences des résidents et des stagiaires post-doctoraux (fellows) en psychiatrie des toxicomanies. Méthodes : Suivant les lignes directrices PRISMA, nous avons effectué une recherche dans cinq bases de données couvrant la période allant de leur création jusqu’à août 2020 pour recenser les études de type évaluation portant sur le développement de compétences en matière de toxicomanie par les résidents et les stagiaires postdoctoraux (fellows) en psychiatrie. Nous avons évalué la qualité des études à l’aide de l’outil d’évaluation du risque de biais de l’Institut Joanna Briggs pour les études observationnelles. Résultats : Dix-sept des 1600 études répertoriées répondaient à nos critères d’inclusion. Les compétences en matière de psychiatrie des toxicomanies couvrent les thèmes de développement des connaissances de base; l’attitude, la communication et les habiletés de leadership; le dépistage, l’évaluation et le diagnostic; la prise en charge; et les populations particulières. Parmi les exemples d’interventions éducatives efficaces visant à améliorer les compétences en matière de toxicomanie figurent les modules portant sur les troubles liés à l’abus de substances et les stages cliniques intégrées qui combinent simultanément plusieurs types d’habiletés. L’expérience concrète vécue semble améliorer l’attitude des apprenants à l’égard de la pratique de la psychiatrie des toxicomanies. Conclusions :  Bien qu’il existe actuellement des preuves à l’appui de stratégies visant à développer les compétences en psychiatrie des toxicomanies, le manque d’étude mesurant le maintien des compétences sur une période de suivi plus longue et l’absence d’essais cliniques randomisés limite la force des preuves de la présente revue.  Les APC qui abordent actuellement la dépendance ne recoupent que partiellement les lignes directrices pour les cursus de formation et le contenu des études recensées dans notre revue. Ces APC doivent être mieux définies pour les programmes d’études et les compétences qu’elles visent doivent être mieux circonscrites pour les résidents et les superviseurs. De surcroît, des évaluations doivent être effectuées pour garantir l’atteinte et le maintien d’une compétence adéquate en matière de toxicomanie

Storm-triggered, increased supply of sediment-derived phosphorus to the epilimnion in a small freshwater lake

This study investigated internal loading of sediment-derived phosphorus (P) in a small, meso-eutrophic lake (surface area 0.2 km2, catchment area 2.7 km2, mean depth 6 m, maximum depth 14 m) on the Atlantic seaboard of western Europe. High resolution data collected over 2.5 years (1 Mar 2011 to 30 Sep 2013) revealed inconsistent patterns in (1) the timing and magnitude of lake turnover and (2) the relative importance of the transfer of hypolimnetic sediment-derived P to the epilimnion when compared with external catchment loading. Lake turnover events during spring and summer had the effect of increasing the internal loading of epilimnetic P during the main growing season, thus adding to eutrophication pressure and contributing to algal blooms in the lake. Abrupt pre-fall (autumnal) turnover events and associated increases in eutrophication pressure such as those reported here may become more frequent occurrences in western Europe because of warming-induced increases in Atlantic summer storm frequency and magnitude, and they could counter the apparent effectiveness of measures aimed at reducing eutrophication impacts through limiting external loadings of nutrients from the catchment

Storm-triggered, increased supply of sediment-derived phosphorus to the epilimnion in a small freshwater lake

This study investigated internal loading of sediment-derived phosphorus (P) in a small, meso-eutrophic lake (surface area 0.2 km2, catchment area 2.7 km2, mean depth 6 m, maximum depth 14 m) on the Atlantic seaboard of western Europe. High resolution data collected over 2.5 years (1 Mar 2011 to 30 Sep 2013) revealed inconsistent patterns in (1) the timing and magnitude of lake turnover and (2) the relative importance of the transfer of hypolimnetic sediment-derived P to the epilimnion when compared with external catchment loading. Lake turnover events during spring and summer had the effect of increasing the internal loading of epilimnetic P during the main growing season, thus adding to eutrophication pressure and contributing to algal blooms in the lake. Abrupt pre-fall (autumnal) turnover events and associated increases in eutrophication pressure such as those reported here may become more frequent occurrences in western Europe because of warming-induced increases in Atlantic summer storm frequency and magnitude, and they could counter the apparent effectiveness of measures aimed at reducing eutrophication impacts through limiting external loadings of nutrients from the catchment

Oxytocin enhances basolateral amygdala activation and functional connectivity while processing emotional faces: preliminary findings in autistic versus non-autistic women

Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala – the brain’s “salience detector” – while processing emotional faces vs. shapes was tested in 16 autistic and 21 non-autistic women by fMRI in a placebo-controlled, within-subjects, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35 voxel cluster, MNI coordinates of peak voxel= -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not non-autistic women (mean change =+0.003%, t=0.153, ptukey=0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin’s effects on the amygdala to specifically include autistic women and specify the subregion of the effect.TLP was supported by the Autism Research Trust, Cambridge Trust, and Natural Sciences and Engineering Research Council of Canada. MVL was supported by an ERC Starting Grant (ERC-2017-STG; 755816). MCL was supported by a Canadian Institutes of Health Research (CIHR) Sex and Gender Science Chair (GSB 171373), the O’Brien Scholars Program within the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children, Toronto, the Academic Scholars Award from the Department of Psychiatry, University of Toronto, the CAMH Foundation, and the Ontario Brain Institute. SBC received funding from the Wellcome Trust 214322\Z\18\Z. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. SBC also received funding from the Autism Centre of Excellence, SFARI, the Templeton World Charitable Fund, the MRC, and the National Institute for Health Research (NIHR). Any views expressed are those of the author(s) and not necessarily those of the funder. RB was supported by the MRC UK, Pinsent Darwin Trust and British Academy post-doctoral fellowship

Evaluating preferences for online psychological interventions to decrease cannabis use in young adults with psychosis : an observational study

Innovative technology-based solutions have the potential to improve access to clinically proven interventions for cannabis use disorder (CUD) in individuals with first episode psychosis (FEP). High patient engagement with app-based interventions is critical for achieving optimal outcomes. 104 individuals 18 to 35 years old with FEP and CUD from three Canadian provinces completed an electronic survey to evaluate preferences for online psychological intervention intensity, participation autonomy, feedback related to cannabis use, and technology platforms and app functionalities. The development of the questionnaire was informed by a qualitative study that included patients and clinicians. We used Best-Worst Scaling (BWS) and item ranking methodologies to measure preferences. Conditional logistic regression models for BWS data revealed high preferences for moderate intervention intensity (e.g., modules with a length of 15 min) and treatment autonomy that included preferences for using technology-based interventions and receiving feedback related to cannabis use once a week. Luce regression models for rank items revealed high preferences for smartphone-based apps, video intervention components, and having access to synchronous communications with clinicians and gamification elements. Results informed the development of iCanChange (iCC), a smartphone-based intervention for the treatment of CUD in individuals with FEP that is undergoing clinical testing

Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis

BACKGROUND: MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis. METHODS AND FINDINGS: By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p , 0.01) and chronic diarrhoea. Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1b, TNF-a, and IFN-c was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-c, TNF-a, and IL-13). This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar accumulation of nonglycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in noninflamed intestinal tissue. Although our study demonstrates that mucin misfolding and ER stress initiate colitis in mice, it does not ascertain the genetic or environmental drivers of ER stress in human colitis. CONCLUSIONS: Characterisation of the mouse models we created and comparison with human disease suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of human colitis and that clinical studies combining genetics, ER stress-related pathology and relevant environmental epidemiology are warranted. The Editors’ Summary of this article follows the references

Prolidase deficiency causes spontaneous T cell activation and lupus-like autoimmunity

Prolidase deficiency (PD) is a multisystem disorder caused by mutations in the PEPD gene, which encodes a ubiquitously expressed metallopeptidase essential for the hydrolysis of dipeptides containing C-terminal proline or hydroxyproline. PD typically presents in childhood with developmental delay, skin ulcers, recurrent infections, and, in some patients, autoimmune features that can mimic systemic lupus erythematosus. The basis for the autoimmune association is uncertain, but might be due to self-antigen exposure with tissue damage, or indirectly driven by chronic infection and microbial burden. In this study, we address the question of causation and show that Pepd-null mice have increased antinuclear autoantibodies and raised serum IgA, accompanied by kidney immune complex deposition, consistent with a systemic lupus erythematosus–like disease. These features are associated with an accumulation of CD4 and CD8 effector T cells in the spleen and liver. Pepd deficiency leads to spontaneous T cell activation and proliferation into the effector subset, which is cell intrinsic and independent of Ag receptor specificity or antigenic stimulation. However, an increase in KLRG1+ effector CD8 cells is not observed in mixed chimeras, in which the autoimmune phenotype is also absent. Our findings link autoimmune susceptibility in PD to spontaneous T cell dysfunction, likely to be acting in combination with immune activators that lie outside the hemopoietic system but result from the abnormal metabolism or loss of nonenzymatic prolidase function. This knowledge provides insight into the role of prolidase in the maintenance of self-tolerance and highlights the importance of treatment to control T cell activation

Reducing cannabis use in young adults with psychosis using iCanChange, a mobile health app : protocol for a pilot randomized controlled trial (ReCAP-iCC)

Background: Cannabis use is the most prevalent among adolescents and young adults; frequent consumption is associated with cannabis use disorder (CUD) and psychosis, with a high prevalence (up to 50%) of CUD in individuals with first-episode psychosis (FEP). Early Intervention Services (EIS) for psychosis include face-to-face psychosocial interventions for CUD, because reducing or discontinuing cannabis use improves clinical and health care service use outcomes. However, multiple barriers (eg, staff availability and limited access to treatment) can hinder the implementation of these interventions. Mobile health (mHealth) interventions may help circumvent some of these barriers; however, to date, no study has evaluated the effects of mHealth psychological interventions for CUD in individuals with FEP. Objective: This study describes the protocol for a pilot randomized controlled trial using a novel mHealth psychological intervention (iCanChange [iCC]) to address CUD in young adults with FEP. iCC was developed based on clinical evidence showing that in individuals without psychosis, integrating the principles of cognitive behavioral therapy, motivational interviewing, and behavioral self-management approaches are effective in improving cannabis use–related outcomes. Methods: Consenting individuals (n=100) meeting the inclusion criteria (eg, aged 18-35 years with FEP and CUD) will be randomly allocated in a 1:1 ratio to the intervention (iCC+modified EIS) or control (EIS) group. The iCC is fully automatized and contains 21 modules that are completed over a 12-week period and 3 booster modules available during the 3-month follow-up period. Validated self-report measures will be taken via in-person assessments at baseline and at 6, 12 (end point), and 24 weeks (end of trial); iCC use data will be collected directly from the mobile app. Primary outcomes are intervention completion and trial retention rates, and secondary outcomes are cannabis use quantity, participant satisfaction, app use, and trial recruiting parameters. Exploratory outcomes include severity of psychotic symptoms and CUD severity. For primary outcomes, we will use the chi-square test using data collected at week 12. We will consider participation in iCC acceptable if ≥50% of the participants complete at least 11 out of 21 intervention modules and the trial feasible if attrition does not reach 50%. We will use analysis of covariance and mixed-effects models for secondary outcomes and generalized estimating equation multivariable analyses for exploratory outcomes. Results: Recruitment began in July 2022, and data collection is anticipated to be completed in July 2024. The main results are expected to be submitted for publication in 2024. We will engage patient partners and other stakeholders in creating a multifaceted knowledge translation plan to reach a diverse audience. Conclusions: If feasible, this study will provide essential data for a larger-scale efficacy trial of iCC on cannabis use outcomes in individuals with FEP and CUD

Generation Times in Wild Chimpanzees and Gorillas Suggest Earlier Divergence Times in Great Ape and Human Evolution

Fossils and molecular data are two independent sources of information that should in principle provide consistent inferences of when evolutionary lineages diverged. Here we use an alternative approach to genetic inference of species split times in recent human and ape evolution that is independent of the fossil record. We first use genetic parentage information on a large number of wild chimpanzees and mountain gorillas to directly infer their average generation times. We then compare these generation time estimates with those of humans and apply recent estimates of the human mutation rate per generation to derive estimates of split times of great apes and humans that are independent of fossil calibration. We date the human–chimpanzee split to at least 7–8 million years and the population split between Neanderthals and modern humans to 400,000–800,000 y ago. This suggests that molecular divergence dates may not be in conflict with the attribution of 6- to 7-million-y-old fossils to the human lineage and 400,000-y-old fossils to the Neanderthal lineage.Human Evolutionary Biolog

Brain activation patterns associated with cue reactivity and craving in abstinent problem gamblers, heavy smokers and healthy controls: an fMRI study

Abnormal cue reactivity is a central characteristic of addiction, associated with increased activity in motivation, attention and memory related brain circuits. In this neuroimaging study, cue reactivity in problem gamblers (PRG) was compared with cue reactivity in heavy smokers (HSM) and healthy controls (HC). A functional magnetic resonance imaging event-related cue reactivity paradigm, consisting of gambling, smoking-related and neutral pictures, was employed in 17 treatment-seeking non-smoking PRG, 18 non-gambling HSM, and 17 non-gambling and non-smoking HC. Watching gambling pictures (relative to neutral pictures) was associated with higher brain activation in occipitotemporal areas, posterior cingulate cortex, parahippocampal gyrus and amygdala in PRG compared with HC and HSM. Subjective craving in PRG correlated positively with brain activation in left ventrolateral prefrontal cortex and left insula. When comparing the HSM group with the two other groups, no significant differences in brain activity induced by smoking cues were found. In a stratified analysis, the HSM subgroup with higher Fagerström Test for Nicotine Dependence scores (FTND M = 5.4) showed higher brain activation in ventromedial prefrontal cortex, rostral anterior cingulate cortex, insula and middle/superior temporal gyrus while watching smoking-related pictures (relative to neutral pictures) than the HSM subgroup with lower FTND scores (FTND M = 2.9) and than non-smoking HC. Nicotine craving correlated with activation in left prefrontal and left amygdala when viewing smoking-related pictures in HSM. Increased regional responsiveness to gambling pictures in brain regions linked to motivation and visual processing is present in PRG, similar to neural mechanisms underlying cue reactivity in substance dependence. Increased brain activation in related fronto-limbic brain areas was present in HSM with higher FTND scores compared with HSM with lower FTND scores